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• W2622292815 endingPage "8608" @default.
• W2622292815 startingPage "8596" @default.
• W2622292815 abstract "The glucocorticoid receptor (GR) is a ligand-regulated transcription factor that controls the expression of extensive gene networks, driving both up- and down-regulation. GR utilizes multiple DNA-binding-dependent and -independent mechanisms to achieve context-specific transcriptional outcomes. The DNA-binding-independent mechanism involves tethering of GR to the pro-inflammatory transcription factor activator protein-1 (AP-1) through protein-protein interactions. This mechanism has served as the predominant model of GR-mediated transrepression of inflammatory genes. However, ChIP-seq data have consistently shown GR to occupy AP-1 response elements (TREs), even in the absence of AP-1. Therefore, the current model is insufficient to explain GR action at these sites. Here, we show that GR regulates a subset of inflammatory genes in a DNA-binding-dependent manner. Using structural biology and biochemical approaches, we show that GR binds directly to TREs via sequence-specific contacts to a GR-binding sequence (GBS) half-site found embedded within the TRE motif. Furthermore, we show that GR-mediated transrepression observed at TRE sites to be DNA-binding-dependent. This represents a paradigm shift in the field, showing that GR uses multiple mechanisms to suppress inflammatory gene expression. This work further expands our understanding of this complex multifaceted transcription factor." @default.
• W2622292815 created "2017-06-15" @default.
• W2622292815 creator A5000602438 @default.
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• W2622292815 creator A5079165413 @default.
• W2622292815 date "2017-06-07" @default.
• W2622292815 modified "2023-10-14" @default.
• W2622292815 title "Tethering not required: the glucocorticoid receptor binds directly to activator protein-1 recognition motifs to repress inflammatory genes" @default.
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• W2622292815 doi "https://doi.org/10.1093/nar/gkx509" @default.
• W2622292815 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5737878" @default.
• W2622292815 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28591827" @default.
• W2622292815 hasPublicationYear "2017" @default.
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